Nucleoside analogues are an important class of therapeutic agents. More particularly, dioxolane nucleoside analogues in which a substituted 1,3-dioxolane is replacing the carbohydrate found in natural nucleoside have shown to have biological activity.
Dioxolane analogues were first reported by Belleau et al. in EP 0337713 published Oct. 19, 1989, in U.S. Pat. No. 5,041,449 issued Aug. 20, 1991 and U.S. Pat. No. 5,270,315 issued Dec. 14, 1993.
9-(β-D-2-hydroxymethyl-1,3-dioxolane-4-yl)-2,6-diaminopurine (β-D-DAPD) and 9-(β-D-hydroxymethyl 1,3-dioxolane-4-yl)-9-guanine (β-D-DXG) have been reported by Gu et al. (Antimicrob. Agents Chemother. (1999), 43(10), pp 2376-2382 and Nucleosides Nucleotides (1999), 18(4&5), pp 891-892) to have useful efficacy against HIV-1 in various cell system.
Additionally, it was also reported (Weitman et al Clinical Cancer Research (2000), 6(4), pp 1574-1578 and Giles et al Journal of Clinical Oncology (2001), 19(3), pp 762-771 and also Gourdeau et al Cancer Chemother. Pharmacol. (2001), 47(3), pp 236-240) that 1-(β-L-2-hydroxymethyl-1,3-dioxolane-4-yl)-cytosine (β-L-OddC, troxacitabine) have shown efficacy for the treatment of various forms of cancers (e.g. solid tumours, adult leukemia and lymphomas).
DAPD and troxacitabine are currently in clinical development. The production of drug compound has to deal with issues such as cost and efficacy, as well as, environmental concerns and management of waste. Although several methods exist for the production of dioxolane nucleoside analogues, there is always a need for further development of new chemical processes for producing such compounds.